1. Technical Field
The present invention relates to preventive, therapeutic and improving agents having affinity for and agonistic action on the thrombopoietin receptor for diseases against which activation of the thrombopoietin receptor is effective. Specifically, it relates to pharmaceutical compositions comprising compounds which increase platelets through stimulation of differentiation and proliferation of hematopoietic stem cells, megakaryocytic progenitor cells and megakaryocytes or compounds for therapeutic angiogenesis or with anti-arteriosclerosis action that stimulate differentiation and proliferation of vascular endothelial cells and endothelial progenitor cells.
2. Background Art
Thrombopoietin is a cytokine consisting of 332 amino acids that increases platelet production by stimulating differentiation and proliferation of hematopoietic stem cells, megakaryocytic progenitor cells and megakaryocytes mediated by its receptor and therefore is promising as a drug for hematological disorders. Recent reports that it stimulates differentiation and proliferation of vascular endothelial cells and endothelial progenitor cells have raised expectations of therapeutic angiogenesis, anti-arteriosclerosis and prevention of cardiovascular events (for example, non-patent document 1, non-patent document 2 and non-patent document 3).
Biologically active substances which have been known so far to regulate platelet production through the thrombopoietin receptor include, in addition to thrombopoietin itself, low molecular weight peptides having affinity for the thrombopoietin receptor (for example, patent document 1, patent document 2, patent document 3 and patent document 4).
As a result of search for nonpeptidic low molecular weight compounds that increase platelet production mediated by the thrombopoietin receptor, low molecular weight compounds having affinity for the thrombopoietin receptor have been reported (for example, patent document 5 to patent document 26).    1) Applications filed by Hokuriku Seiyaku Co., Ltd. relating to 1,4-benzodiazepine derivatives (patent documents 5 and 6)    2) International Laid-open Patent Applications filed by Shionogi & Co., Ltd. (patent documents 7-10)    3) International Laid-open Patent Applications filed by SmithKline Beecham Corp (patent documents 11-19)    4) Japanese Laid-open Patent Application filed by Torii Pharmaceutical Co., Ltd. (patent document 20)    5) International Laid-open Patent Application, filed by Roche Diagnostics GMBH (patent document 21)    6) International Laid-open Patent Application filed by Yamanouchi Pharmaceutical Co., Ltd. (patent document 22 and 23)    7) Japanese Laid-open Patent Application filed by Japan Tabacco Inc. (patent document 24)    8) Japanese Laid-open Patent Applications filed by Nissan Chemical Industries, Ltd. (patent documents 25 and 26)    Patent document 1 JP-A-10-72492    Patent document 2 WO96/40750    Patent document 3 WO96/40189    Patent document 4 WO98/25965    Patent document 5 JP-A-11-1477    Patent document 6 JP-A-11-152276    Patent document 7 WO01/07423    Patent document 8 WO01/53267    Patent document 9 WO02/059099    Patent document 10 WO02/059100    Patent document 11 WO00/35446    Patent document 12 WO00/66112    Patent document 13 WO01/34585    Patent document 14 WO01/17349    Patent document 15 WO01/39773    Patent document 16 WO01/21180    Patent document 17 WO01/89457    Patent document 18 WO02/49413    Patent document 19 WO02/085343    Patent document 20 JP-A-2001-97948    Patent document 21 WO99/11262    Patent document 22 WO02/062775    Patent document 23 WO03/062233    Patent document 24 JP-A-2003-238565    Patent document 25 WO04/033433    Patent document 26 WO04/108683    Non-patent document 1 Microvasc. Res., 1999: 58, p. 108-113    Non-patent document 2 Circ. Res., 1999: 84, p. 785-796    Non-patent document 3 Blood 2001:98, p. 71a-72a